Immunology of Physical Exercise: Is Equus caballus an Appropriate Animal Model for Human Athletes?
Abstract: Domestic horses routinely participate in vigorous and various athletic activities. This enables the horse to serve as a model for studying athletic physiology and immunology in other species, including humans. For instance, as a model of physical efforts, such as endurance rides (long-distance running/aerobic exercise) and races (anaerobic exercise), the horse can be useful in evaluating post-exercise response. Currently, there has been significant interest in finding biomarkers, which characterize the advancement of training and adaptation to physical exercise in the horse. The parallels in cellular responses to physical exercises, such as changes in receptor expression and blood cell activity, improve our understanding of the mechanisms involved in the body's response to intense physical activity. This study focuses on the changes in levels of the pro- and anti-inflammatory cytokines and cellular response in the context of post-exercise immune response. Both the direction of changes in cytokine levels and cellular responses of the body, such as proliferation and expression of surface markers on lymphocytes, monocytes and neutrophils, show cross-functional similarities. This review reveals that horses are robust research models for studying the immune response to physical exercise in human athletes.
Publication Date: 2024-05-10 PubMed ID: 38791248PubMed Central: PMC11121269DOI: 10.3390/ijms25105210Google Scholar: Lookup
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- Journal Article
- Review
Summary
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The article discusses the use of horses, specifically Equus caballus, as valuable models for studying the immune response to physical exercise in humans due to the similarities in the body’s cellular and hormonal responses to intense training.
Emphasis on Horse as an Animal Model
- The article initially emphasizes the suitability of the domestic horse as a model organism for athletics. The authors highlight the relevance of this model due to the variety and intensity of athletic activities horses commonly participate in, similar to human sports.
- The question of whether a horse is an appropriate model for human athletes is introduced with a focus on studying cellular responses and biochemical changes related to different forms of physical exercise.
Understanding Physical Efforts
- The paper uses horses for modeling various forms of physical exercise, focusing specifically on long-distance running (aerobic exercise) and races (anaerobic exercise).
- The authors discuss these variations of physical exercises and their distinct impact on the post-exercise response, which can provide an understanding of how the human body might react under similar stressful situations.
Exploration of Biomarkers
- There is a notable mention of the interest in identifying biomarkers that could monitor training progress and adaptation in horses. Finding such markers could be helpful for human athletes as well, providing a measurable indication of the physiological changes occurring due to training and exercise.
Pro- and Anti-inflammatory Cytokines
- The core of the study revolves around changes in pro- and anti-inflammatory cytokines, which are small proteins released by cells that have a specific effect on the interactions and communications between cells.
- The authors emphasize the correlation between the levels of these cytokines and the cellular immune response after exercise.
Cellular Responses during Exercise
- In addition to hormonal changes, the paper highlights the change in expression of surface markers on lymphocytes, monocytes, and neutrophils (types of white blood cells), which are integral to the immune response.
- These cellular responses offer another dimension of understanding the impact of strenuous physical activity on the body and immune system.
Final Findings
- The conclusion from reviewing relevant literature is that horses are a robust and relevant model for studying the immune response to physical exercise in human athletes due to considerable similarities in cellular and hormonal responses.
Cite This Article
APA
Witkowska-Piłaszewicz O, Malin K, Dąbrowska I, Grzędzicka J, Ostaszewski P, Carter C.
(2024).
Immunology of Physical Exercise: Is Equus caballus an Appropriate Animal Model for Human Athletes?
Int J Mol Sci, 25(10), 5210.
https://doi.org/10.3390/ijms25105210 Publication
Researcher Affiliations
- Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
- Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland.
- Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland.
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, Poland.
- Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, KY 40506, USA.
MeSH Terms
- Animals
- Horses / immunology
- Humans
- Physical Conditioning, Animal
- Athletes
- Cytokines / metabolism
- Models, Animal
- Exercise / physiology
- Biomarkers
Grant Funding
- 2021/41/B/NZ7/03548 / National Science Center
Conflict of Interest Statement
The authors declare no conflicts of interest.
References
This article includes 186 references
- Lee E.C., Fragala M.S., Kavouras S.A., Queen R.M., Pryor J.L., Casa D.J.. Biomarkers in Sports and Exercise: Tracking Health, Performance, and Recovery in Athletes. J. Strength Cond. Res. 2017;31:2920–2937.
- Ericsson A.C., Crim M.J., Franklin C.L.. A brief history of animal modeling. Mo. Med. 2013;110:201–205.
- Sarrafian T.L., Garcia T.C., Dienes E.E., Murphy B., Stover S.M., Galuppo L.D.. A Nonterminal Equine Mandibular Model of Bone Healing. Vet. Surg. 2015;44:314–321.
- Smith R.K., Garvican E.R., Fortier L.A.. The current ‘state of play’ of regenerative medicine in horses: What the horse can tell the human. Regen. Med. 2014;9:673–685.
- Brehm W., Burk J., Delling U.. Application of Stem Cells for the Treatment of Joint Disease in Horses. 2014. pp. 215–228. Methods in Molecular Biology.
- McIlwraith C.W., Frisbie D.D., Kawcak C.E.. The horse as a model of naturally occurring osteoarthritis. Bone Jt. Res. 2012;1:297–309.
- Patterson-Kane J.C., Becker D.L., Rich T.. The Pathogenesis of Tendon Microdamage in Athletes: The Horse as a Natural Model for Basic Cellular Research. J. Comp. Pathol. 2012;147:227–247.
- Iwamoto J., Takeda T.. Stress fractures in athletes: Review of 196 cases. J. Orthop. Sci. 2003;8:273–278.
- Välimäki V.V., Alfthan H., Lehmuskallio E., Löyttyniemi E., Sahi T., Suominen H., Välimäki M.J.. Risk factors for clinical stress fractures in male military recruits: A prospective cohort study. Bone. 2005;37:267–273.
- Witkowska-Piłaszewicz O., Bąska P., Czopowicz M., Żmigrodzka M., Szarska E., Szczepaniak J., Nowak Z., Winnicka A., Cywińska A.. Anti-Inflammatory State in Arabian Horses Introduced to the Endurance Training. Animals 2019;9:616.
- Witkowska-Piłaszewicz O., Pingwara R., Winnicka A.. The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses. Antioxidants 2020;9:1155.
- Horohov D.W.. The equine immune responses to infectious and allergic disease: A model for humans?. Mol. Immunol. 2015;66:89–96.
- Hinchcliff K.W., Kaneps A.J., Geor R.J.. Equine Exercise Physiology: The Science of Exercise in the Athletic Horse. 2008. 463p.
- Scheffer D.d.L., Latini A.. Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs. Biochim. Et Biophys. Acta (BBA)—Mol. Basis Dis. 2020;1866:165823.
- Kakanis M., Peake J., Hooper S., Gray B., Marshall-Gradisnik S.. The open window of susceptibility to infection after acute exercise in healthy young male elite athletes. J. Sci. Med. Sport. 2010;13:e85–e86.
- Campbell J.P., Turner J.E.. Debunking the Myth of Exercise-Induced Immune Suppression: Redefining the Impact of Exercise on Immunological Health across the Lifespan. Front. Immunol. 2018;9:648.
- Gleeson M., Bishop N., Oliveira M., McCauley T., Tauler P., Muhamad A.S.. Respiratory infection risk in athletes: Association with antigen-stimulated IL-10 production and salivary IgA secretion. Scand. J. Med. Sci. Sports. 2012;22:410–417.
- Shaw D.M., Merien F., Braakhuis A., Dulson D.. T-cells and their cytokine production: The anti-inflammatory and immunosuppressive effects of strenuous exercise. Cytokine 2018;104:136–142.
- Folsom R.W., Littlefield-Chabaud M.A., French D.D., Pourciau S.S., Mistric L., Horohov D.W.. Exercise alters the immune response to equine influenza virus and increases susceptibility to infection. Equine Vet. J. 2001;33:664–669.
- Carvallo F.R., Uzal F.A., Diab S.S., Hill A.E., Arthur R.M.. Retrospective study of fatal pneumonia in racehorses. J. Vet. Diagn. Investig. 2017;29:450–456.
- Raidal S., Love D., Bailey G.. Effect of a single bout of high intensity exercise on lower respiratory tract contamination in the horse. Aust. Vet. J. 1997;75:293–295.
- Wood J.L.N., Newton J.R., Chanter N., Mumford J.A.. Association between Respiratory Disease and Bacterial and Viral Infections in British Racehorses. J. Clin. Microbiol. 2005;43:120–126.
- Mårtensson S., Nordebo K., Malm C.. High Training Volumes are Associated with a Low Number of Self-Reported Sick Days in Elite Endurance Athletes. J. Sports Sci. Med. 2014;13:929–933.
- Pedersen B.K., Saltin B.. Exercise as medicine—Evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand. J. Med. Sci. Sports. 2015;25:1–72.
- Nieman D.C., Henson D.A., Austin M.D., Sha W.. Upper respiratory tract infection is reduced in physically fit and active adults. Br. J. Sports Med. 2011;45:987–992.
- Hoffman J.. Physiological Aspects of Sport Training and Performance. 2014. 505p.
- Gleeson L.E., Sheedy F.J.. Metabolic reprogramming & inflammation: Fuelling the host response to pathogens. Semin. Immunol. 2016;28:450–468.
- da Silveira M.P., da Silva Fagundes K.K., Bizuti M.R., Starck É., Rossi R.C., de Resende e Silva D.T.. Physical exercise as a tool to help the immune system against COVID-19: An integrative review of the current literature. Clin. Exp. Med. 2021;21:15–28.
- Horohov D.W., Sinatra S.T., Chopra R.K., Jankowitz S., Betancourt A., Bloomer R.J.. The Effect of Exercise and Nutritional Supplementation on Proinflammatory Cytokine Expression in Young Racehorses during Training. J. Equine Vet. Sci. 2012;32:805–815.
- McKeever K.H., Arent S.M., Davitt P.. The Athletic Horse. 2014. Endocrine and immune responses to exercise and training; pp. 88–107.
- Silveira L.S., Antunes B.d.M.M., Minari A.L.A., dos Santos R.V.T., Neto J.C.R., Lira F.S.. Macrophage Polarization: Implications on Metabolic Diseases and the Role of Exercise. Crit. Rev. Eukaryot. Gene Expr. 2016;26:115–132.
- Arfuso F., Giannetto C., Fazio F., Panzera F., Piccione G.. Training Program Intensity Induces an Acute Phase Response in Clinically Healthy Horses. J. Equine Vet. Sci. 2020;88:102986.
- Kaspar F., Jelinek H.F., Perkins S., Al-Aubaidy H.A., DeJong B., Butkowski E.. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study. Mediat. Inflamm. 2016;2016:5474837.
- Allen J., Sun Y., Woods J.A.. Progress in Molecular Biology and Translational Science. 2015. Exercise and the Regulation of Inflammatory Responses; pp. 337–354.
- Cerqueira É., Marinho D.A., Neiva H.P., Lourenço O.. Inflammatory Effects of High and Moderate Intensity Exercise—A Systematic Review. Front. Physiol. 2020;10:1550.
- Witkowska-Piłaszewicz O., Bąska P., Czopowicz M., Żmigrodzka M., Szczepaniak J., Szarska E., Winnicka A., Cywińska A.. Changes in Serum Amyloid A (SAA) Concentration in Arabian Endurance Horses during First Training Season. Animals 2019;9:330.
- Cywinska A., Witkowski L., Szarska E., Schollenberger A., Winnicka A.. Serum amyloid A (SAA) concentration after training sessions in Arabian race and endurance horses. BMC Vet. Res. 2013;9:91.
- Siqueira R.F.d., Fernandes W.R.. Post-ride inflammatory markers in endurance horses. Cienc. Rural. 2016;46:1256–1261.
- Cywińska A., Szarska E., Górecka R., Witkowski L., Hecold M., Bereznowski A., Schollenberger A., Winnicka A.. Acute phase protein concentrations after limited distance and long distance endurance rides in horses. Res. Vet. Sci. 2012;93:1402–1406.
- Grzędzicka J., Dąbrowska I., Malin K., Witkowska-Piłaszewicz O.. Exercise-related changes in the anabolic index (testosterone to cortisol ratio) and serum amyloid A concentration in endurance and racehorses at different fitness levels. Front. Vet. Sci. 2023;10:1148990.
- Giori L., Moretti P., Giordano A., Paltrinieri S.. Short-term Evaluation of Serum Amyloid A after Exercise in Clinically Healthy Horses. J. Equine Vet. Sci. 2011;31:499–501.
- Kristensen L., Buhl R., Nostell K., Bak L., Petersen E., Lindholm M., Jacobsen S.. Acute exercise does not induce an acute phase response (APR) in Standardbred trotters. Can. J. Vet. Res. 2014;78:97–102.
- Turło A., Cywińska A., Czopowicz M., Witkowski L., Jaśkiewicz A., Winnicka A.. Racing Induces Changes in the Blood Concentration of Serum Amyloid A in Thoroughbred Racehorses. J. Equine Vet. Sci. 2016;36:15–18.
- Fedewa M.V., Hathaway E.D., Ward-Ritacco C.L.. Effect of exercise training on C reactive protein: A systematic review and meta-analysis of randomised and non-randomised controlled trials. Br. J. Sports Med. 2017;51:670–676.
- Mihelić K., Vrbanac Z., Bojanić K., Kostanjšak T., Ljubić B.B., Gotić J., Vnuk D., Bottegaro N.B.. Changes in Acute Phase Response Biomarkers in Racing Endurance Horses. Animals 2022;12:2993.
- di Masi A., De Simone G., Ciaccio C., D’Orso S., Coletta M., Ascenzi P.. Haptoglobin: From hemoglobin scavenging to human health. Mol. Asp. Med. 2020;73:100851.
- Lippi G., Sanchis-Gomar F.. Epidemiological, biological and clinical update on exercise-induced hemolysis. Ann. Transl. Med. 2019;7:270.
- Davidson R., Robertson J., Galea G., Maughan R.. Hematological Changes Associated with Marathon Running. Int. J. Sports Med. 1987;8:19–25.
- Olaf Schumacher Y., Schmid A., Grathwohl D., Bültermann D., Berg A.. Hematological indices and iron status in athletes of various sports and performances. Med. Sci. Sports Exerc. 2002;34:869–875.
- Binnie M.J., Dawson B., Pinnington H., Landers G., Peeling P.. Part 2: Effect of Training Surface on Acute Physiological Responses after Sport-Specific Training. J. Strength Cond. Res. 2013;27:1057–1066.
- Masini A.P., Tedeschi D., Baragli P., Sighieri C., Lubas G.. Exercise-induced intravascular haemolysis in standardbred horses. Comp. Clin. Pathol. 2003;12:45–48.
- Cywinska A., Szarska E., Kowalska A., Ostaszewski P., Schollenberger A.. Gender differences in exercise-induced intravascular haemolysis during race training in thoroughbred horses. Res. Vet. Sci. 2011;90:133–137.
- Docherty S., Harley R., McAuley J.J., Crowe L.A.N., Pedret C., Kirwan P.D., Siebert S., Millar N.L.. The effect of exercise on cytokines: Implications for musculoskeletal health: A narrative review. BMC Sports Sci. Med. Rehabil. 2022;14:5.
- Liburt N.R., Adams A.A., Betancourt A., Horohov D.W., McKeever K.H.. Exercise-induced increases in inflammatory cytokines in muscle and blood of horses. Equine Vet. J. 2010;42:280–288.
- Sohail M.U., Al-Mansoori L., Al-Jaber H., Georgakopoulos C., Donati F., Botrè F., Sellami M., Elrayess M.A.. Assessment of Serum Cytokines and Oxidative Stress Markers in Elite Athletes Reveals Unique Profiles Associated with Different Sport Disciplines. Front. Physiol. 2020;11:600888.
- Lee H.G., Choi J.-Y., Park J.-W., Park T.S., Song K.-D., Shin D., Cho B.-W.. Effects of exercise on myokine gene expression in horse skeletal muscles. Asian-Australas. J. Anim. Sci. 2019;32:350–356.
- Pedersen B.K., Åkerström T.C.A., Nielsen A.R., Fischer C.P.. Role of myokines in exercise and metabolism. J. Appl. Physiol. 2007;103:1093–1098.
- Ostrowski K., Rohde T., Zacho M., Asp S., Pedersen B.K.. Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running. J. Physiol. 1998;508:949–953.
- Barbosa L.P., da Silva Aguiar S., Santos P.A., dos Santos Rosa T., Maciel L.A., de Deus L.A., Neves R.V.P., de Araújo Leite P.L., Gutierrez S.D., Sousa C.V.. Relationship between inflammatory biomarkers and testosterone levels in male master athletes and non-athletes. Exp. Gerontol. 2021;151:111407.
- Baum M., Klöpping-Menke K., Müller-Steinhardt M., Liesen H.. Increased concentrations of interleukin 1-β in whole blood cultures supernatants after 12 weeks of moderate endurance exercise. Eur. J. Appl. Physiol. 1999;79:500–503.
- Plisak U., Szczepaniak J., Żmigrodzka M., Giercuszkiewicz-Hecold B., Witkowska-Piłaszewicz O.. Changes in novel anti-infalmmatory cytokine concetration in the bood of endurance and race horses at different levels of training. Comput. Struct. Biotechnol. J. 2023;21:418–424.
- Moldoveanu A.I., Shephard R.J., Shek P.N.. The Cytokine Response to Physical Activity and Training. Sports Med. 2001;31:115–144.
- Cywińska A., Turło A., Witkowski L., Szarska E., Winnicka A.. Changes in blood cytokine concentrations in horses after long-distance endurance rides. Med. Weter. 2014;70:568–571.
- Nielsen H.G., Øktedalen O., Opstad P.-K., Lyberg T.. Plasma Cytokine Profiles in Long-Term Strenuous Exercise. J. Sports Med. 2016;2016:7186137.
- Carey A.L., Febbraio M.A.. Interleukin-6 and insulin sensitivity: Friend or foe?. Diabetologia. 2004;47:1135–1142.
- Fischer C.P.. Interleukin-6 in acute exercise and training: What is the biological relevance?. Exerc. Immunol. Rev. 2006;12:6–33.
- Pedersen B.K., Febbraio M.A.. Muscle as an endocrine organ: Focus on muscle-derived interleukin-6. Physiol. Rev. 2008;88:1379–1406.
- Sugama K., Suzuki K., Yoshitani K., Shiraishi K., Kometani T.. IL-17, neutrophil activation and muscle damage following endurance exercise. Exerc. Immunol. Rev. 2012;18:116–127.
- Peake J.M., Della Gatta P., Suzuki K., Nieman D.C.. Cytokine expression and secretion by skeletal muscle cells: Regulatory mechanisms and exercise effects. Exerc. Immunol. Rev. 2015;21:8–25.
- Margeli A., Skenderi K., Tsironi M., Hantzi E., Matalas A.-L., Vrettou C., Kanavakis E., Chrousos G., Papassotiriou I.. Dramatic Elevations of Interleukin-6 and Acute-Phase Reactants in Athletes Participating in the Ultradistance Foot Race Spartathlon: Severe Systemic Inflammation and Lipid and Lipoprotein Changes in Protracted Exercise. J. Clin. Endocrinol. Metab. 2005;90:3914–3918.
- Brenner I.K.M., Natale V.M., Vasiliou P., Moldoveanu A.I., Shek P.N., Shephard R.J.. Impact of three different types of exercise on components of the inflammatory response. Eur. J. Appl. Physiol. 1999;80:452–460.
- Natelson B.H., Zhou X., Ottenweller J.E., Bergen M.T., Sisto S.A., Drastal S., Tapp W.N., Gause W.L.. Effect of Acute Exhausting Exercise on Cytokine Gene Expression in Men. Int. J. Sports Med. 1996;17:299–302.
- Garbers C., Heink S., Korn T., Rose-John S.. Interleukin-6: Designing specific therapeutics for a complex cytokine. Nat. Rev. Drug Discov. 2018;17:395–412.
- Bury T., Louis R., Radermecker M., Pirnay F.. Blood Mononudear Cells Mobilization and Cytokines Secretion during Prolonged Exercises. Int. J. Sports Med. 1996;17:156–160.
- Sprenger H., Jacobs C., Nain M., Gressner A.M., Prinz H., Wesemann W., Gemsa D.. Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running. Clin. Immunol. Immunopathol. 1992;63:188–195.
- Suzuki K., Yamada M., Kurakake S., Okamura N., Yamaya K., Liu Q., Kudoh S., Kowatari K., Nakaji S., Sugawara K.. Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans. Eur. J. Appl. Physiol. 2000;81:281–287.
- Ullum H., Haahr P.M., Diamant M., Palmo J., Halkjaer-Kristensen J., McGinnis G.R., Ballmann C., Peters B., Nanayakkara G., Roberts M.. Bicycle exercise enhances plasma IL-6 but does not change IL-1 alpha, IL-1 beta, IL-6, or TNF-alpha pre-mRNA in BMNC. J. Appl. Physiol. 1994;77:93–97.
- Smith L.L.. Cytokine hypothesis of overtraining: A physiological adaptation to excessive stress?. Med. Sci. Sports Exerc. 2000;32:317.
- Starkie R.L., Rolland J., Angus D.J., Anderson M.J., Febbraio M.A.. Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-α levels after prolonged running. Am. J. Physiol. Physiol. 2001;280:C769–C774.
- Page A.E., Stewart J.C., Fielding C.L., Horohov D.W.. The Effect of a 160-Kilometer Competitive Endurance Ride on Inflammatory Marker mRNA Expression in Horses. J. Equine Vet. Sci. 2019;79:45–49.
- Londhe P., Davie J.K.. Interferon-γ Resets Muscle Cell Fate by Stimulating the Sequential Recruitment of JARID2 and PRC2 to Promoters to Repress Myogenesis. Sci. Signal. 2013;6:ra107.
- LaVoy E.C., Bosch J.A., Lowder T.W., Simpson R.J.. Acute aerobic exercise in humans increases cytokine expression in CD27− but not CD27+ CD8+ T-cells. Brain Behav. Immun. 2013;27:54–62.
- Farrar M.A., Schreiber R.D.. The Molecular Cell Biology of Interferon-γ and its Receptor. Annu. Rev. Immunol. 1993;11:571–611.
- Svensson M., Lexell J., Deierborg T.. Effects of Physical Exercise on Neuroinflammation, Neuroplasticity, Neurodegeneration, and Behavior: What We Can Learn From Animal Models in Clinical Settings. Neurorehabilit. Neural Repair. 2015;29:577–589.
- Wadley A.J., Chen Y.-W., Lip G.Y., Fisher J.P., Aldred S.. Low volume–high intensity interval exercise elicits antioxidant and anti-inflammatory effects in humans. J. Sports Sci. 2016;34:1–9.
- Ostrowski K., Rohde T., Asp S., Schjerling P., Pedersen B.K.. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J. Physiol. 1999;515:287–291.
- Steensberg A., Fischer C.P., Keller C., Møller K., Pedersen B.K.. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am. J. Physiol. Endocrinol. Metab. 2003;285:E433–E437.
- Rosa T.S., Neves R.V.P., Deus L.A., Sousa C.V., da Silva S., de Souza M.K., Moraes M.R., Rosa É.C.C.C., Andrade R.V., Korhonen M.T.. Sprint and endurance training in relation to redox balance, inflammatory status and biomarkers of aging in master athletes. Nitric Oxide 2020;102:42–51.
- Hart P.H., Vitti G.F., Burgess D.R., Whitty G.A., Piccoli D.S., Hamilton J.A.. Potential antiinflammatory effects of interleukin 4: Suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2. Proc. Natl. Acad. Sci. USA. 1989;86:3803–3807.
- Pedersen B.K., Toft A.D.. Effects of exercise on lymphocytes and cytokines. Br. J. Sports Med. 2000;34:246–251.
- Heredia J.E., Mukundan L., Chen F.M., Mueller A.A., Deo R.C., Locksley R.M., Rando T.A., Chawla A.. Type 2 Innate Signals Stimulate Fibro/Adipogenic Progenitors to Facilitate Muscle Regeneration. Cell. 2013;153:376–388.
- te Velde A.A., Huijbens R.J., de Vries J.E., Figdor C.G.. IL-4 decreases Fc gamma R membrane expression and Fc gamma R-mediated cytotoxic activity of human monocytes. J. Immunol. 1990;144:3046–3051.
- Moyna N., Acker G., Fulton J., Weber K., Goss F., Robertson R., Tollerud D., Rabin B.. Lymphocyte Function and Cytokine Production during Incremental Exercise in Active and Sedentary Males and Females. Int. J. Sports Med. 1996;17:585–591.
- Miglio A., Cappelli K., Capomaccio S., Mecocci S., Silvestrelli M., Antognoni M.T.. Metabolic and Biomolecular Changes Induced by Incremental Long-Term Training in Young Thoroughbred Racehorses during First Workout Season. Animals 2020;10:317.
- Della Gatta P.A., Garnham A.P., Peake J.M., Cameron-Smith D.. Effect of exercise training on skeletal muscle cytokine expression in the elderly. Brain Behav. Immun. 2014;39:80–86.
- Prokopchuk O., Liu Y., Wang L., Wirth K., Schmidtbleicher D., Steinacker J.M.. Skeletal muscle IL-4, IL-4Ralpha, IL-13 and IL-13Ralpha1 expression and response to strength training. Exerc. Immunol. Rev. 2007;13:67–75.
- Knudsen N.H., Stanya K.J., Hyde A.L., Chalom M.M., Alexander R.K., Liou Y.-H., Starost K.A., Gangl M.R., Jacobi D., Liu S.. Interleukin-13 drives metabolic conditioning of muscle to endurance exercise. Science 2020;368:eaat3987.
- Wilson J., De Donato M., Appelbaum B., Garcia C.T., Peters S.. Differential Expression of Innate and Adaptive Immune Genes during Acute Physical Exercise in American Quarter Horses. Animals 2023;13:308.
- Cappelli K., Amadori M., Mecocci S., Miglio A., Antognoni M.T., Razzuoli E.. Immune Response in Young Thoroughbred Racehorses under Training. Animals 2020;10:1809.
- Page A.E., Adam E., Arthur R., Barker V., Franklin F., Friedman R., Grande T., Hardy M., Howard B., Partridge E.. Expression of select mRNA in Thoroughbreds with catastrophic racing injuries. Equine Vet. J. 2022;54:63–73.
- Guo Y., Xiao P., Lei S., Deng F., Xiao G.G., Liu Y., Chen X., Li L., Wu S., Chen Y.. How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochim. Biophys. Sin. 2008;40:426–436.
- Davis M.S., Malayer J.R., Vandeventer L., Royer C.M., McKenzie E.C., Williamson K.K.. Cold weather exercise and airway cytokine expression. J. Appl. Physiol. 2005;98:2132–2136.
- Gabriel H., Schwarz L., Steffens G., Kindermann W.. Immunoregulatory Hormones, Circulating Leucocyte and Lymphocyte Subpopulations before and after Endurance Exercise of Different Intensities. Int. J. Sports Med. 1992;13:359–366.
- Walsh N.P., Gleeson M., Shephard R.J., Gleeson M., Woods J.A., Bishop N.C., Fleshner M., Green C., Pedersen B.K., Hoffman-Goetz L.. Position Statement Part one: Immune function and exercise. Exerc. Immunol. Rev. 2011;17:6–63.
- Cuniberti B., Badino P., Odore R., Girardi C., Re G.. Effects induced by exercise on lymphocyte β-adrenergic receptors and plasma catecholamine levels in performance horses. Res. Vet. Sci. 2012;92:116–120.
- Malinowski K., Kearns C.F., Guirnalda P.D., Roegner V., McKeever K.H.. Effect of chronic clenbuterol administration and exercise training on immune function in horses. J. Anim. Sci. 2004;82:3500–3507.
- Nieman D.C.. Exercise, Infection, and Immunity. Int. J. Sports Med. 1994;15:S131–S141.
- Nesse L.L., Johansen G.I., Blom A.K.. Effects of racing on lymphocyte proliferation in horses. Am. J. Vet. Res. 2002;63:528–530.
- Peake J.M., Neubauer O., Walsh N.P., Simpson R.J.. Recovery of the immune system after exercise. J. Appl. Physiol. 2017;122:1077–1087.
- Siedlik J.A., Benedict S.H., Landes E.J., Weir J.P., Vardiman J.P., Gallagher P.M.. Acute bouts of exercise induce a suppressive effect on lymphocyte proliferation in human subjects: A meta-analysis. Brain Behav. Immun. 2016;56:343–351.
- Pedersen B.K., Ullum H.. NK cell response to physical activity: Possible mechanisms of action. Med. Sci. Sports Exerc. 1994;26:140–146.
- Kurcz E.V., Lawrence L.M., Kelley K.W., Miller P.A.. The effect of intense exercise on the cell-mediated immune response of horses. J. Equine Vet. Sci. 1988;8:237–239.
- Nielsen H.B., Pedersen B.K.. Lymphocyte proliferation in response to exercise. Eur. J. Appl. Physiol. 1997;75:375–379.
- Shinkai S., Kohno H., Kimura K., Komura T., Asai H., Inai R., Oka K., Kurokawa Y., Shephard R.J.. Physical activity and immune senescence in men. Med. Sci. Sports Exerc. 1995;27:1516–1526.
- Simpson R.J., Spielmann G., Hanley P., Bollard C.M.. A single bout of exercise augments the expansion of multi-virus specific T-cells in healthy humans. Brain Behav. Immun. 2014;40:e51.
- Hines M.T., Schott H.C. II, Bayly W.M., Leroux A.J.. Exercise and Immunity: A Review with Emphasis on the Horse. J. Vet. Intern. Med. 1996;10:280–289.
- Kajiura J.S., MacDougall J.D., Ernst P.B., Younglai E.V.. Immune response to changes in training intensity and volume in runners. Med. Sci. Sports Exerc. 1995;27:1111–1117.
- McCarthy D.A., Dale M.M.. The Leucocytosis of Exercise: A Review and Model. Sports Med. 1988;6:333–363.
- Tvede N., Kappel M., Halkjœr-Kristensen J., Galbo H., Pedersen B.K.. The Effect of Light, Moderate and Severe Bicycle Exercise on Lymphocyte Subsets, Natural and Lymphokine Activated Killer Cells, Lymphocyte Proliferative Response and Interleukin 2 Production. Int. J. Sports Med. 1993;14:275–282.
- Witkowska-Piłaszewicz O., Pingwara R., Szczepaniak J., Winnicka A.. The Effect of the Clenbuterol—β2-Adrenergic Receptor Agonist on the Peripheral Blood Mononuclear Cells Proliferation, Phenotype, Functions, and Reactive Oxygen Species Production in Race Horses In Vitro. Cells 2021;10:936.
- Hamza E., Gerber V., Steinbach F., Marti E.. Equine CD4+ CD25high T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro. Immunology 2011;134:292–304.
- Perry C., Pick M., Bdolach N., Hazan-Halevi I., Kay S., Berr I., Reches A., Harishanu Y., Grisaru D.. Endurance Exercise Diverts the Balance between Th17 Cells and Regulatory T Cells. PLoS ONE 2013;8:e74722.
- Rehm K., Sunesara I., Marshall G.D.. Increased Circulating Anti-inflammatory Cells in Marathon-trained Runners. Int. J. Sports Med. 2015;36:832–836.
- Robbin M.G., Wagner B., Noronha L.E., Antczak D.F., de Mestre A.M.. Subpopulations of equine blood lymphocytes expressing regulatory T cell markers. Vet. Immunol. Immunopathol. 2011;140:90–101.
- Timmons B.W., Cieslak T.. Human natural killer cell subsets and acute exercise: A brief review. Exerc. Immunol. Rev. 2008;14:8–23.
- Zimmer P., Schenk A., Kieven M., Holthaus M., Lehmann J., Lövenich L., Bloch W.. Exercise induced alterations in NK-cell cytotoxicity—Methodological issues and future perspectives. Exerc. Immunol. Rev. 2017;23:66–81.
- Hsia J.-Y., Chen J.-T., Chen C.-Y., Hsu C.-P., Miaw J., Huang Y.-S., Yang C.-Y.. Prognostic significance of intratumoral natural killer cells in primary resected esophageal squamous cell carcinoma. Chang Gung Med. J. 2005;28:335–340.
- Llavero F., Alejo L.B., Fiuza-Luces C., López Soto A., Valenzuela P.L., Castillo-García A., Morales J.S., Fernández D., Aldazabal I.P., Ramírez M.. Exercise training effects on natural killer cells: A preliminary proteomics and systems biology approach. Exerc. Immunol. Rev. 2021;27:125–141.
- Rincón H.G., Solomon G.F., Benton D., Rubenstein L.Z.. Exercise in frail elderly men decreases natural killer cell activity. Aging Clin. Exp. Res. 1996;8:109–112.
- Zouhal H., Jacob C., Delamarche P., Gratas-Delamarche A.. Catecholamines and the Effects of Exercise, Training and Gender. Sports Med. 2008;38:401–423.
- Moro-García M.A., Fernández-García B., Echeverría A., Rodríguez-Alonso M., Suárez-García F.M., Solano-Jaurrieta J.J., López-Larrea C., Alonso-Arias R.. Frequent participation in high volume exercise throughout life is associated with a more differentiated adaptive immune response. Brain Behav. Immun. 2014;39:61–74.
- Viveiros M.M., Antczak D.F.. Characterization of equine natural killer and IL-2 stimulated lymphokine activated killer cell populations. Dev. Comp. Immunol. 1999;23:521–532.
- Lunn D.P., Schram B.R., Vagnoni K.E., Schobert C.S., Horohov D.W., Ginther O.J.. Positive selection of EqCD8+ precursors increases equine lymphokine-activated killing. Vet. Immunol. Immunopathol. 1996;53:1–13.
- Horohov D.. Equine Exercise Physiology. 2008. Immunological responses to exercise and training; pp. 410–422.
- Ziegler-Heitbrock L., Ancuta P., Crowe S., Dalod M., Grau V., Hart D.N., Leenen P.J.M., Liu Y.-J., MacPherson G., Randolph G.J.. Nomenclature of monocytes and dendritic cells in blood. Blood 2010;116:e74–e80.
- Narasimhan P.B., Marcovecchio P., Hamers A.A.J., Hedrick C.C.. Nonclassical Monocytes in Health and Disease. Annu. Rev. Immunol. 2019;37:439–456.
- Kiku Y., Kusano K.-I., Miyake H., Fukuda S., Takahashi J., Inotsume M., Hirano S., Yoshihara T., Toribio R.E., Okada H.. Flow Cytometric Analysis of Peripheral Blood Mononuclear Cells Induced by Experimental Endotoxemia in Horse. J. Vet. Med. Sci. 2003;65:857–863.
- Sarkar S., Chelvarajan L., Go Y.Y., Cook F., Artiushin S., Mondal S., Anderson K., Eberth J., Timoney P.J., Kalbfleisch T.S.. Equine Arteritis Virus Uses Equine CXCL16 as an Entry Receptor. J. Virol. 2016;90:3366–3384.
- Gibbons N., Goulart M.R., Chang Y.-M., Efstathiou K., Purcell R., Wu Y., Peters L.M., Turmaine M., Szladovits B., Garden O.A.. Phenotypic heterogeneity of peripheral monocytes in healthy dogs. Vet. Immunol. Immunopathol. 2017;190:26–30.
- Blanks A.M., Wagamon T.T., Lafratta L., Sisk M.G., Senter M.B., Pedersen L.N., Bohmke N., Shah A., Mihalick V.L., Franco R.L.. Impact of physical activity on monocyte subset CCR2 expression and macrophage polarization following moderate intensity exercise. Brain Behav. Immun.—Health 2020;2:100033.
- Steppich B., Dayyani F., Gruber R., Lorenz R., Mack M., Ziegler-Heitbrock H.W.L.. Selective mobilization of CD14+CD16+ monocytes by exercise. Am. J. Physiol. Physiol. 2000;279:C578–C586.
- Timmerman K.L., Flynn M.G., Coen P.M., Markofski M.M., Pence B.D.. Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: A role in the anti-inflammatory influence of exercise?. J. Leukoc. Biol. 2008;84:1271–1278.
- Cupps T.R., Fauci A.S.. Corticosteroid-Mediated Immunoregulation in Man. Immunol. Rev. 1982;65:133–155.
- Miglio A., Falcinelli E., Mezzasoma A.M., Cappelli K., Mecocci S., Gresele P., Antognoni M.T.. Effect of First Long-Term Training on Whole Blood Count and Blood Clotting Parameters in Thoroughbreds. Animals 2021;11:447.
- Moghadam-Kia S., Oddis C.V., Aggarwal R.. Approach to asymptomatic creatine kinase elevation. Clevel. Clin. J. Med. 2016;83:37–42.
- Marqués-Jiménez D., Calleja-González J., Arratibel I., Delextrat A., Terrados N.. Are compression garments effective for the recovery of exercise-induced muscle damage? A systematic review with meta-analysis. Physiol. Behav. 2016;153:133–148.
- Bekkelund S.I., Johnsen S.H.. Creatine kinase is associated with reduced inflammation in a general population: The Tromsø study. PLoS ONE 2018;13:e0198133.
- Baird M.F., Graham S.M., Baker J.S., Bickerstaff G.F.. Creatine-Kinase- and Exercise-Related Muscle Damage Implications for Muscle Performance and Recovery. J. Nutr. Metab. 2012;2012:960363.
- Paillot R., Hannant D., Kydd J., Daly J.. Vaccination against equine influenza: Quid novi?. Vaccine 2006;24:4047–4061.
- Craigo J.K., Leroux C., Howe L., Steckbeck J.D., Cook S.J., Issel C.J., Montelaro R.C.. Transient immune suppression of inapparent carriers infected with a principal neutralizing domain-deficient equine infectious anaemia virus induces neutralizing antibodies and lowers steady-state virus replication. J. Gen. Virol. 2002;83:1353–1359.
- Leroux C., Montelaro R.C., Cadoré J.-L.. Equine Infectious Anemia Virus (EIAV): What has HIV’s country cousin got to tell us?. Vet. Res. 2004;35:485–512.
- Capomaccio S., Cappelli K., Spinsanti G., Mencarelli M., Muscettola M., Felicetti M., Supplizi A.V., Bonifazi M.. Athletic humans and horses: Comparative analysis of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) expression in peripheral blood mononuclear cells in trained and untrained subjects at rest. BMC Physiol. 2011;11:3.
- Harris M.D.. Infectious Disease in Athletes. Curr. Sports Med. Rep. 2011;10:84–89.
- Karagianni A.E., Lisowski Z.M., Hume D.A., Scott Pirie R.. The equine mononuclear phagocyte system: The relevance of the horse as a model for understanding human innate immunity. Equine Vet. J. 2021;53:231–249.
- Wilke M.M., Nydam D.V., Nixon A.J.. Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model. J. Orthop. Res. 2007;25:913–925.
- Godwin E.E., Young N.J., Dudhia J., Beamish I.C., Smith R.K.W.. Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet. J. 2012;44:25–32.
- Halaris A.E., Belendiuk K.T., Freedman D.X.. Antidepressant drugs affect dopamine uptake. Biochem. Pharmacol. 1975;24:1896–1898.
- Malda J., Benders K.E.M., Klein T.J., de Grauw J.C., Kik M.J.L., Hutmacher D.M., Saris D.B.F., van Weeren P.R., Dhert W.J.A.. Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyles. Osteoarthr. Cartil. 2012;20:1147–1151.
- Goodrich L.R., Nixon A.J.. Medical treatment of osteoarthritis in the horse—A review. Vet. J. 2006;171:51–69.
- Nelson B.B., Goodrich L.R., Barrett M.F., Grinstaff M.W., Kawcak C.E.. Use of contrast media in computed tomography and magnetic resonance imaging in horses: Techniques, adverse events and opportunities. Equine Vet. J. 2017;49:410–424.
- Nelson B.B., Kawcak C.E., Barrett M.F., McIlwraith C.W., Grinstaff M.W., Goodrich L.R.. Recent advances in articular cartilage evaluation using computed tomography and magnetic resonance imaging. Equine Vet. J. 2018;50:564–579.
- Dudhia J., Scott C.M., Draper E.R.C., Heinegård D., Pitsillides A.A., Smith R.K.. Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell. 2007;6:547–556.
- Mokone G.G., Gajjar M., September A.V., Schwellnus M.P., Greenberg J., Noakes T.D., Collins M.. The Guanine-Thymine Dinucleotide Repeat Polymorphism within the Tenascin-C Gene is Associated with Achilles Tendon Injuries. Am. J. Sports Med. 2005;33:1016–1021.
- Mokone G.G., Schwellnus M.P., Noakes T.D., Collins M.. The COL5A1 gene and Achilles tendon pathology. Scand. J. Med. Sci. Sports. 2006;16:19–26.
- Tully L.J., Murphy A.M., Smith R.K.W., Hulin-Curtis S.L., Verheyen K.L.P., Price J.S.. Polymorphisms in TNC and COL5A1 genes are associated with risk of superficial digital flexor tendinopathy in National Hunt Thoroughbred racehorses. Equine Vet. J. 2014;46:289–293.
- Coleman S.J., Zeng Z., Hestand M.S., Liu J., Macleod J.N.. Analysis of Unannotated Equine Transcripts Identified by mRNA Sequencing. PLoS ONE 2013;8:e70125.
- Raudsepp T., Finno C.J., Bellone R.R., Petersen J.L.. Ten years of the horse reference genome: Insights into equine biology, domestication and population dynamics in the post-genome era. Anim. Genet. 2019;50:569–597.
- Simpson R.J., Kunz H., Agha N., Graff R.. Progress in Molecular Biology and Translational Science. 2015. Exercise and the Regulation of Immune Functions; pp. 355–380.
- Suzuki K., Totsuka M., Nakaji S., Yamada M., Kudoh S., Liu Q., Sugawara K., Yamaya K., Sato K.. Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage. J. Appl. Physiol. 1999;87:1360–1367.
- Andriichuk A., Tkachenko H.. Effect of gender and exercise on haematological and biochemical parameters in Holsteiner horses. J. Anim. Physiol. Anim. Nutr. 2017;101:e404–e413.
- Gatti R., De Palo E.F.. An update: Salivary hormones and physical exercise. Scand. J. Med. Sci. Sports. 2011;21:157–169.
- Hill E.E., Zack E., Battaglini C., Viru M., Viru A., Hackney A.C.. Exercise and circulating Cortisol levels: The intensity threshold effect. J. Endocrinol. Investig. 2008;31:587–591.
- Kirschbaum C., Hellhammer D.H.. Salivary cortisol in psychoneuroendocrine research: Recent developments and applications. Psychoneuroendocrinology 1994;19:313–333.
- Witkowska-Piłaszewicz O., Grzędzicka J., Seń J., Czopowicz M., Żmigrodzka M., Winnicka A., Cywińska A., Carter C.. Stress response after race and endurance training sessions and competitions in Arabian horses. Prev. Vet. Med. 2021;188:105265.
- Zamani A., Salehi I., Alahgholi-Hajibehzad M.. Moderate Exercise Enhances the Production of Interferon-γ and Interleukin-12 in Peripheral Blood Mononuclear Cells. Immune Netw. 2017;17:186–191.
- Suzuki K., Nakaji S., Kurakake S., Totsuka M., Sato K., Kuriyama T., Fujimoto H., Shibusawa K., Machida K., Sugawara K.. Exhaustive exercise and type-1/type-2 cytokine balance with special focus on interleukin-12 p40/p70. Exerc. Immunol. Rev. 2003;9:48–57.
- Luk H.-Y., Levitt D.E., Lee E.C., Ganio M.S., McDermott B.P., Kupchak B.R., McFarlin B.K., Hill D.W., Armstrong L.E., Vingren J.L.. Pro- and anti-inflammatory cytokine responses to a 164-km road cycle ride in a hot environment. Eur. J. Appl. Physiol. 2016;116:2007–2015.
- MacDonald C., Wojtaszewski J.F.P., Pedersen B.K., Kiens B., Richter E.A.. Interleukin-6 release from human skeletal muscle during exercise: Relation to AMPK activity. J. Appl. Physiol. 2003;95:2273–2277.
- Mach N., Ramayo-Caldas Y., Clark A., Moroldo M., Robert C., Barrey E., López J.M., Le Moyec L.. Understanding the response to endurance exercise using a systems biology approach: Combining blood metabolomics, transcriptomics and miRNomics in horses. BMC Genom. 2017;18:187.
- Bernecker C., Scherr J., Schinner S., Braun S., Scherbaum W.A., Halle M.. Evidence for an exercise induced increase of TNF-α and IL-6 in marathon runners. Scand. J. Med. Sci. Sports. 2013;23:207–214.
- Lefkowitz R.J.. Identification of adenylate cyclase-coupled beta-adrenergic receptors with radiolabeled beta-adrenergic antagonists. Biochem. Pharmacol. 1975;24:1651–1658.
- Eriksson B., Hedfors E.. The Effect of Adrenaline, Insulin and Hydrocortisone on Human Peripheral Blood Lymphocytes Studied by Cell Surface Markers. Scand. J. Haematol. 1977;18:121–128.
- Crary B., Hauser S.L., Borysenko M., Kutz I., Hoban C., Ault K.A., Weiner H.L., Benson H.. Epinephrine-induced changes in the distribution of lymphocyte subsets in peripheral blood of humans. J. Immunol. 1983;131:1178–1181.
- Rumpf C., Proschinger S., Schenk A., Bloch W., Lampit A., Javelle F., Zimmer P.. The Effect of Acute Physical Exercise on NK-Cell Cytolytic Activity: A Systematic Review and Meta-Analysis. Sports Med. 2021;51:519–530.
- Gavrieli R., Ashlagi-Amiri T., Eliakim A., Nemet D., Zigel L., Berger-Achituv S., Falk B., Wolach B.. The effect of aerobic exercise on neutrophil functions. Med. Sci. Sports Exerc. 2008;40:1623–1628.
- Wong C.W., Smith S.E., Thong Y.H., Opdebeeck J.P., Thornton J.R.. Effects of exercise stress on various immune functions in horses. Am. J. Vet. Res. 1992;53:1414–1417.
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